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We experimentally and theoretically investigate the thermal conductivity and mechanical properties of polycrystalline HKUST-1 metal-organic frameworks (MOFs) infiltrated with three guest molecules: tetracyanoquinodimethane (TCNQ), 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F 4 -TCNQ), and (cyclohexane-1,4-diylidene)dimalononitrile (H 4 -TCNQ). This allows for modification of the interaction strength between the guest and host, presenting an opportunity to study the fundamental atomic scale mechanisms of how guest molecules impact the thermal conductivity of large unit cell porous crystals. The thermal conductivities of the guest@MOF systems decrease significantly, by on average a factor of 4, for all infiltrated samples as compared to the uninfiltrated, pristine HKUST-1. This reduction in thermal conductivity goes in tandem with an increase in density of 38% and corresponding increase in heat capacity of ∼48%, defying conventional effective medium scaling of thermal properties of porous materials. We explore the origin of this reduction by experimentally investigating the guest molecules' effects on the mechanical properties of the MOF and performing atomistic simulations to elucidate the roles of the mass and bonding environments on thermal conductivity. The reduction in thermal conductivity can be ascribed to an increase in vibrational scattering introduced by extrinsic guest-MOF collisions as well as guest molecule-induced modifications to the intrinsic vibrational structure of the MOF in the form of hybridization of low frequency modes that is concomitant with an enhanced population of localized modes. The concentration of localized modes and resulting reduction in thermal conductivity do not seem to be significantly affected by the mass or bonding strength of the guest species.

Background: Perineural invasion (PNI) and lymphovascular invasion (LVI) may be adverse prognostic indicators in squamous cell carcinoma (SCC) of the tongue., Methods: The percentages of histological PNI and LVI were determined in 335 patients with tongue SCC. Sixty tumours originally reported as negative for these features were tested to determine how many more were positive with "immunohistochemical enhancement.", Results: PNI was found in 141 (42.1%) and LVI in 51 (15.2%) patients. 79.4% of the 141 patients who had PNI and 72.6% of the 51 with LVI had a T3 or T4 tumour. Lymph node metastasis was identified in 145 (51.2%) of the 280 patients who had undergone neck dissection; 58.2% of the 141 patients with PNI and 80.4% of the 51 patients with LVI had lymph node metastasis. There was a highly statistically significant correlation between PNI with increasing pT (P < .00001) and pN (P < .0001) stage, and a statistically significant correlation between LVI and pT stage (P < .001), the association of LVI with pN status could not be reliably tested statistically. Immunohistochemistry for S100 identified five further cases of PNI, but review of the original H&E showed the feature was present in four and had been missed at original reporting. CD31 identified three further possible cases of LVI and D2-40 none. The endothelium of some vascular channels was positive for both CD31 and D2-40 and cross-reactivity with other cells compromised interpretation., Conclusions: Histological identification of PNI and LVI per se remains of uncertain prognostic significance. "Immunohistochemical enhancement" offered little benefit., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cystic squamous cell carcinomas (SCCs) of the jaws, including carcinoma cuniculatum, are rare, slow growing, and relentlessly invasive. The aim of this article is to present 12 cases, 4 of which were designated as carcinoma cuniculatum on the basis of deeply endophytic, anastomosing channels of cystic stratified squamous epithelium and keratin microabscesses. The other 8 were also cystic, but more heterogeneous morphologically and were diagnosed as well differentiated SCCs. Six patients were female, 6 were male (mean age = 74.0 years, range = 50-94 years). Six tumors affected the mandible, 6 the maxillary alveolus with or without extension into the hard palate. All patients underwent primary resection with neck dissection and were staged as T4a N0 M0. In 4 patients, diagnosis was delayed as a result of superficial biopsies and/or confusing histopathology. Cystic SCCs of the jaws can be difficult to diagnose and clinicoradiological correlation is essential. Long-term follow-up is mandatory.

In this series, there are 8 typical verruciform xanthomas of the oral mucosa and 3 anomalies, 1 polypoid, 1 florid, and 1 carcinomatous. All were characterized by infiltrates of CD68-positive xanthomatous histiocytes in the lamina propria. The 11 patients comprised 6 men and 5 women (mean age = 54.5 years, range = 40-69). Both keratinized and nonkeratinized sites were affected. A history of lichenoid inflammation was recorded in 5 patients. The polypoid xanthoma presented in a woman aged 54 years as a polyp of the labial commissure. The florid lesion affected the dorsum of the tongue of a man aged 54 years and at 20 mm was the largest of the 11 lesions, but the only one with candidal infection. The squamous cell carcinoma manifested as a papilloverrucous hyperkeratosis of the palatal gingiva in a man aged 69 years. The latter 2 (and 1 "typical" verruciform xanthoma) required re-excision, but none has since recurred.

We propose a strategy to potentially best enhance interfacial thermal transport through solid-solid interfaces by adding nano-engineered, exponentially mass-graded intermediate layers. This exponential design rule results in a greater enhancement than a linearly mass-graded interface. By combining calculations using non-equilibrium Green's functions (NEGF) and non-equilibrium molecular dynamics (NEMD), we investigated the role of impedance matching and anharmonicity in the enhancement in addition to geometric parameters such as the number of layers and the junction thickness. Our analysis shows that the effect on thermal conductance is dominated by the phonon thermalization through anharmonic effects, while elastic phonon transmission and impedance matching play a secondary role. In the harmonic limit, increasing the number of layers results in greater elastic phonon transmission at each individual boundary, countered by the decrease of available conducting channels. Consequently, conductance initially increases with number of layers due to improved bridging, but quickly saturates. The presence of slight anharmonic effects (at very low temperature, T = 2 K) turns the saturation into a monotonically increasing trend. Anharmonic effects can further facilitate interfacial thermal transport through the thermalization of phonons at moderate temperatures. At high temperature, however, the role of anharmonicity as a facilitator of interfacial thermal transport reverses. Strong anharmonicity introduces significant intrinsic resistance, overruling the enhancement in thermal conduction at the boundaries. It follows that at a particular temperature, there exists a corresponding junction thickness at which thermal conductance is maximized.

Spectral linewidths are used to assess a variety of physical properties, even as spectral overlap makes quantitative extraction difficult owing to uncertainty. Uncertainty, in turn, can be minimized with the choice of appropriate experimental conditions used in spectral collection. In response, we assess the experimental factors dictating uncertainty in the quantification of linewidth from a Raman experiment highlighting the comparative influence of (1) spectral resolution, (2) signal to noise, and (3) relative peak intensity (RPI) of the overlapping peaks. Practically, Raman spectra of SiGe thin films were obtained experimentally and simulated virtually under a variety of conditions. RPI is found to be the most impactful parameter in specifying linewidth followed by the spectral resolution and signal to noise. While developed for Raman experiments, the results are generally applicable to spectroscopic linewidth studies illuminating the experimental trade-offs inherent in quantification.

Our aim was to find out first whether the extrinsic muscles of the tongue are histologically identifiable, and secondly to what degree the use of the new criteria in the 8th editions of the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control (UICC) manuals (which have recognised the importance of depth of invasion of tumour, rather than invasion of the extrinsic muscles of the tongue and extranodal extension), will alter staging of lingual squamous cell carcinoma (SCC). The histological sections from 165 patients who had had primary resection of lingual SCC were reviewed, and one or more extrinsic muscles of the tongue was identified in 100 patients (61%), with the genioglossus seen the most often (in 96). By contrast, the hyoglossus was identified in only eight patients, the styloglossus in two, and the palatoglossus in none. Identification was straightforward only in extensive resections. Applying the criteria from the 8th edition increased the number of pT3 SCC with a simultaneous reduction in pT4a tumours. The number of pN2b SCC was also reduced, but the new category of pN3b meant that overall 53% of tumours were upstaged. The kappa scores for agreement between the two sets of criteria were 0.221 (weighted 0.410) for the pT values, 0.508 (0.713) for pN values (but 0.227, weighted 0.386, if the pN0 values were removed before calculation), and 0.243 (0.514) for overall stage, indicating poor to fair agreement. We conclude that the removal of invasion of extrinsic muscles of the tongue as a criterion for a pT4a SCC is justified, and that many SCC of the tongue will be upstaged as a result of implementation of the 8th editions., (Copyright © 2017 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Aim: To determine how many ameloblastomas were misdiagnosed as dentigerous cysts (DCs) by correlating the radiological and histopathological features of a series of both entities., Methods and Results: Histopathology reports and radiological imaging of 135 DCs and 43 ameloblastomas were reviewed. Any clinical or radiological feature that suggested that the diagnosis of DC was wrong-for example, absence of an unerupted tooth-prompted review of the original histology. A total of 34 cases coded as DC at diagnosis were excluded; in the remaining 101 patients, the clinicoradiological and histopathological features were consistent with DC in 96 (95.0%). Review of the histology revealed that 4 patients had actually had odontogenic keratocysts (OKCs) and one a luminal/simple unicystic ameloblastoma (UA). One other OKC and 3 other ameloblastomas (1 luminal UA, 2 solid/multicystic) had originally been diagnosed as DC; these had been identified prior to the study. Of the 9 misdiagnosed patients, 6 were ≤20 years old. Clinically, DC had been the only, or one of the differential, diagnoses in 7 patients; in the other 2, the clinical diagnosis was radicular cyst. In none of the 4 misdiagnosed ameloblastomas was the radiology compatible with a diagnosis of DC. Incorrect terminology had been used on the histopathology request form in 5 of the 34 excluded cases where the clinical diagnosis was DC, despite the cyst being periapical to an erupted carious or root-filled tooth., Conclusions: The entire clinical team must ensure that a histopathological diagnosis of DC is consistent with the clinicoradiological scenario, particularly in younger patients.

A method is presented to constrain a statistical model of sub-gridcolumn moisture variability using high-resolution satellite cloud data. The method can be used for large-scale model parameter estimation or cloud data assimilation. The gridcolumn model includes assumed probability density function (PDF) intra-layer horizontal variability and a copula-based inter-layer correlation model. The observables used in the current study are Moderate Resolution Imaging Spectroradiometer (MODIS) cloud-top pressure, brightness temperature and cloud optical thickness, but the method should be extensible to direct cloudy radiance assimilation for a small number of channels. The algorithm is a form of Bayesian inference with a Markov chain Monte Carlo (MCMC) approach to characterizing the posterior distribution. This approach is especially useful in cases where the background state is clear but cloudy observations exist. In traditional linearized data assimilation methods, a subsaturated background cannot produce clouds via any infinitesimal equilibrium perturbation, but the Monte Carlo approach is not gradient-based and allows jumps into regions of non-zero cloud probability. The current study uses a skewed-triangle distribution for layer moisture. The article also includes a discussion of the Metropolis and multiple-try Metropolis versions of MCMC.

Part 1 of this series presented a Monte Carlo Bayesian method for constraining a complex statistical model of global circulation model (GCM) sub-gridcolumn moisture variability using high-resolution Moderate Resolution Imaging Spectroradiometer (MODIS) cloud data, thereby permitting parameter estimation and cloud data assimilation for large-scale models. This article performs some basic testing of this new approach, verifying that it does indeed reduce mean and standard deviation biases significantly with respect to the assimilated MODIS cloud optical depth, brightness temperature and cloud-top pressure and that it also improves the simulated rotational-Raman scattering cloud optical centroid pressure (OCP) against independent (non-assimilated) retrievals from the Ozone Monitoring Instrument (OMI). Of particular interest, the Monte Carlo method does show skill in the especially difficult case where the background state is clear but cloudy observations exist. In traditional linearized data assimilation methods, a subsaturated background cannot produce clouds via any infinitesimal equilibrium perturbation, but the Monte Carlo approach allows non-gradient-based jumps into regions of non-zero cloud probability. In the example provided, the method is able to restore marine stratocumulus near the Californian coast, where the background state has a clear swath. This article also examines a number of algorithmic and physical sensitivities of the new method and provides guidance for its cost-effective implementation. One obvious difficulty for the method, and other cloud data assimilation methods as well, is the lack of information content in passive-radiometer-retrieved cloud observables on cloud vertical structure, beyond cloud-top pressure and optical thickness, thus necessitating strong dependence on the background vertical moisture structure. It is found that a simple flow-dependent correlation modification from Riishojgaard provides some help in this respect, by better honouring inversion structures in the background state.

It has been more than a decade since the thermal conductivity of vertically aligned carbon nanotube (VACNT) arrays was reported possible to exceed that of the best thermal greases or phase change materials by an order of magnitude. Despite tremendous prospects as a thermal interface material (TIM), results were discouraging for practical applications. The primary reason is the large thermal contact resistance between the CNT tips and the heat sink. Here we report a simultaneous sevenfold increase in in-plane thermal conductivity and a fourfold reduction in the thermal contact resistance at the flexible CNT-SiO2 coated heat sink interface by coupling the CNTs with orderly physical overlapping along the horizontal direction through an engineering approach (shear pressing). The removal of empty space rapidly increases the density of transport channels, and the replacement of the fine CNT tips with their cylindrical surface insures intimate contact at CNT-SiO2 interface. Our results suggest horizontally aligned CNT arrays exhibit remarkably enhanced in-plane thermal conductivity and reduced out-of-plane thermal conductivity and thermal contact resistance. This novel structure makes CNT film promising for applications in chip-level heat dissipation. Besides TIM, it also provides for a solution to anisotropic heat spreader which is significant for eliminating hot spots.

Purpose: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is an independent predictor of poor prognosis. As PNI is not always identified with routine histology, a surrogate marker of PNI would improve detection and better inform treatment planning. The chemokines fractalkine (CX3CL1) and its receptor (CX3CR1) have shown such potential in other cancers, but have yet to be investigated with respect to PNI in oral SCC., Methods: Thirty SCCs of the tongue in which PNI was identified histologically, and 30 in which it was not, were stained for fractalkine and fractalkine receptor using polyclonal antibodies and an immunoperoxidase technique. Tumours were assessed as either positive or negative; no attempt was made to subjectively assess staining intensity or extent., Results: Both markers labelled myofibroblasts in the stroma surrounding the tumour, various neural components, leucocytes, endothelium and salivary myoepithelial cells. Fractalkine also labelled salivary ductal epithelium, vascular smooth muscle and 12/30 SCC which showed PNI. Eight of 30 positive SCCs in which PNI was not identified were also positive for this marker. There was no statistically significant association between fractalkine staining and PNI (p = 0.273). No SCC was positive for fractalkine receptor, but immune dendritic cells within tumour islands were strongly positive, as was striated muscle., Conclusions: Neither fractalkine nor fractalkine receptor is a reliable surrogate marker of PNI in lingual SCC.

The 3ω technique has become a popular method for determining the thermophysical properties of microscale and bulk materials. The prerequisite fabrication of a highly linear metal line a few hundred nanometers thick on the sample can be a failing point in specific material systems. This difficulty can be overcome by utilizing a bidirectional experimental geometry that employs a contact resistance between the sample and heating wire, which also allows for data collection under varying axial pressure loads. In this work, such a system is demonstrated with an emphasis on developing a thermal mount that will optimize sensitivity to the thermophysical parameters of interest: the sample's thermal conductivity, volumetric heat capacity, and the contact resistance between the sample and mount. A general thermal model is presented that can be simplified to analyze nearly any similar system. This model is then employed to analyze a sample in the mounting scheme described with varying applied pressures to demonstrate the general feasibility of the system.

The deep circumflex iliac artery (DCIA) flap is often used for mandibular reconstruction but it is bulky and causes additional donor-site morbidity because of the inclusion of an "obligatory internal oblique muscle". Large composite segmental mandibular resections that consist of floor of mouth, subtotal tongue, and adjacent facial skin are a challenge in terms of reconstruction. They often require 2 free flaps or a free scapular flap and both have disadvantages. The deep circumflex iliac artery perforator (DCIAP) flap with a cutaneous component overcomes the disadvantages. We describe reconstructions with DCIAP flaps in 3 patients with large mandibular composite segmental defects. We report our experience of the flap and discuss some of the difficulties we encountered and the points we learned perioperatively., (Copyright © 2013. Published by Elsevier Ltd.)

Despite a larger sensitivity to temperature as compared to other microscale thermometry methods, Raman based measurements typically have greater uncertainty. In response, a new implementation of Raman thermometry is presented having lower uncertainty while also reducing the time and hardware needed to perform the experiment. Using a modulated laser to excite the Raman response, the intensity of only a portion of the total Raman signal is leveraged as the thermometer by using a single element detector monitored with a lock-in amplifier. Implementation of the lock-in amplifier removes many sources of noise that are present in traditional Raman thermometry where the use of cameras preclude a modulated approach. To demonstrate, the portion of the Raman spectrum that is most advantageous for thermometry is first identified by highlighting, via both numerical prediction and experiment, those spectral windows having the largest linear dependence on temperature. Using such windows, the new technique, termed single element Raman thermometry (SERT), is utilized to measure the thermal profile of an operating microelectromechanical systems (MEMS) device and compared to results obtained with a traditional Raman approach. The SERT method is shown to reduce temperature measurement uncertainty by greater than a factor of 2 while enabling 3 times as many data points to be taken in an equal amount of time as compared to traditional Raman thermometry.

Substitutional solid solutions that exist in both ordered and disordered states will exhibit markedly different physical properties depending on their exact crystallographic configuration. Many random substitutional solid solutions (alloys) will display a tendency to order given the appropriate kinetic and thermodynamic conditions. Such order-disorder transitions will result in major crystallographic reconfigurations, where the atomic basis, symmetry, and periodicity of the alloy change dramatically. Consequently, the dominant scattering mechanism in ordered alloys will be different than that in disordered alloys. In this study, we present a hypothesis that ordered alloys can exhibit lower thermal conductivities than their disordered counterparts at elevated temperatures. To validate this hypothesis, we investigate the phononic transport properties of disordered and ordered AB Lennard-Jones alloys via non-equilibrium molecular dynamics and harmonic lattice dynamics calculations. It is shown that the thermal conductivity of an ordered alloy is the same as the thermal conductivity of the disordered alloy at ≈0.6T(melt) and lower than that of the disordered alloy above 0.8T(melt).

Self-assembled monolayers (SAMs) have recently garnered much interest due to their unique electrical, chemical, and thermal properties. Several studies have focused on thermal transport across solid-SAM junctions, demonstrating that interface conductance is largely insensitive to changes in SAM length. In the present study, we have investigated the vibrational spectra of alkanedithiol-based SAMs as a function of the number of methylene groups forming the molecular backbone via Hartree-Fock methods. In the case of Au-alkanedithiol junctions, it is found that despite the addition of nine new vibrational modes per added methylene group, only one of these modes falls below the maximum phonon frequency of Au. In addition, the alkanedithiol one-dimensional density of normal modes (modes per unit energy per unit length) is nearly constant regardless of chain length, explaining the observed insensitivity. Furthermore, we developed a diffusive transport model intended to predict interface conductance at solid-SAM junctions. It is shown that this predictive model is in an excellent agreement with prior experimental data available in the literature., (© 2011 American Institute of Physics.)

In this open-label, randomized, multiple-dose, two-treatment crossover study, 24 postmenopausal women with moderate to severe atrophic vaginitis received 0.3 mg conjugated estrogens daily for 14 days: 7 days orally (0.3 mg tablet) and 7 days vaginally (0.5 g cream). Steady-state plasma concentrations of E2 and estrone were one-third lower after vaginal versus oral administration of conjugated estrogens., (Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine pharmacokinetic profiles of two times a day and three times a day dosage regimens of Endometrin, a micronized progesterone vaginal insert for luteal support in assisted reproductive technology, compared with a gel., Design: A single-center, randomized, open-label, single-day, and multiple-day (5 days) parallel design pharmacokinetic study., Setting: University clinical research unit., Patient(s): Three groups of six healthy subjects, ages 18 to 40 years., Intervention(s): Endometrin vaginal inserts two times a day or three times a day, or gel daily., Main Outcome Measure(s): Pharmacokinetic profiles., Result(s): Progesterone serum concentrations increased rapidly following administration of Endometrin vaginal insert, producing higher peak concentrations (Cmax) and clearing faster than gel. On the single day of dosing, mean Cmax was 17.0+/-2.7 ng/mL in the two times a day group, 19.8+/-2.9 ng/mL in the three times a day group, and 6.82+/-1.69 ng/mL in the gel group. Endometrin treatments reached steady state within the first 2 days (24-36 hours), much more rapidly than the gel, which had not reached steady state by 5 days. At 5 days, the Endometrin treatments produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours., Conclusions: Endometrin vaginal inserts reached higher Cmax, produced greater systemic exposure (area under the curve 0-24), achieved steady state more rapidly, and cleared more rapidly after termination of therapy than the comparator., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Malakoplakia that presents in the head and neck is rare. We describe a case in a man who presented with a fungating mass in the periauricular skin that was thought to be a malignant tumour. Histopathological and microbiological investigations established a diagnosis of malakoplakia., (Copyright 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

The reduction in size and the increase in speed of opto- and magnetoelectronic devices is making the probability of nonequilibrium electron-phonon phenomena greater, leading to increased thermal resistance in these devices. The measurement of electron-phonon coupling in materials in these devices is becoming increasingly important for accurate thermal management. Here femtosecond thermoreflectance is used to measure the electron-phonon coupling factor in thin Ni films of varying thickness grown on Si and glass substrates. The thermoreflectance response is measured at 1.3 and 1.55 eV, yielding drastically different responses due to the Fermi-level transition at 1.3 eV in Ni. The influence of this transition on the thermoreflectance response results in a measurement of the electron-phonon coupling factor that is twice as high as that recorded in previous measurements that were unaffected by the Fermi-level transition.

With a focus on low-cost and low-power consumption, a miniature laser-induced fluorescence (LIF) detection system was assembled using a 635 nm red diode laser as the excitation source and a photodiode element coupled with an operational amplifier for signal collection. The primary elements of the miniature system, namely the laser and the detection system, cost a combined $70 and required only 270 mW of power for operation. When compared to conventional systems assembled using an argon-ion laser source and a photomultiplier tube, this represents a 98% decrease in the cost, and greater than 5000-fold decrease in power consumption. Quantitation of DNA on microdevices using the miniature LIF detection system was also performed with an error of less than 15%. This detection system is a step in the direction of commercializing microfluidic instrumentation by reducing the cost and power required for operation.

Effective microchip extraction of deoxyribonucleic acid (DNA) from crude biological matrixes has been demonstrated using silica beads or hybrid phases composed of beads and sol-gel. However, the use of monolithic sol-gels alone for extraction of human genomic DNA has been more difficult to define. Here we describe, for the first time, the successful use of monolithic tetramethyl orthosilicate-based sol-gels for effective micro-solid-phase extraction (muSPE) of DNA in a glass microchip format. A functional monolithic silica phase with micrometer-scale pores in the silica matrix resulted from addition of poly(ethylene glycol), a poragen, to the precursor mixture. This allowed a monolithic sol-gel bed to be established in a microchip channel that provided large surface area for DNA extraction with little flow-induced back pressure. DNA extraction efficiencies for simple systems (lambda-phage DNA) were approximately 85%, while efficiencies for the reproducible extraction of human genomic DNA from complex biological matrixes (human blood) were approximately 70%. Blockage of the sol-gel pores by components in the lysed blood was observed in repeat extraction on a single device as a decrease in the extraction efficiency. The developed muSPE protocol was further evaluated to show applicability to clinical samples and bacterial cultures, through extraction of PCR-amplifiable DNA.

Background: Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone therapy as DRSP /17-beta estradiol (DRSP/E2). Because of a significant aldosterone antagonist activity, we studied the effects of DRSP/E2 on serum potassium (K) and blood pressure (BP) in hypertensive postmenopausal women with and without diabetes mellitus., Methods: This was a multicenter trial in postmenopausal women 44 to 70 years of age, either with type 2 diabetes mellitus (n = 82) or without type 2 diabetes mellitus (n = 148) and using an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor antagonist. Patients were randomized to 28 days of DRSP/E2 or placebo. Study endpoints were the number and percentage subjects who developed hyperkalemia (K >or= 5.5 mEq/L) and changes from baseline in clinic systolic and diastolic BP. To increase the likelihood of unmasking hyperkalemia, the nondiabetic group was also administered ibuprofen for 5 days., Results: There were no statistical differences in the overall number and percentage of subjects with hyperkalemia for DRSP/E2 versus placebo. No subject had symptoms or electrocardiographic changes related to hyperkalemia. Blood pressure was reduced by -8.6/-5.8 mm Hg in patients receiving DRSP/E2 versus -3.7/-2.9 mm Hg in those receiving placebo (P < .01 for both SBP and DBP)., Conclusions: In hypertensive postmenopausal women, treatment with DRSP/E2 was not associated with a greater incidence of hyperkalemia than with placebo in patients with and without type 2 diabetes mellitus and concomitant use of ACE inhibitors, angiotensin receptor antagonists, or ibuprofen. Furthermore, DRSP/E2 was found to have a significant antihypertensive effect in this high-risk population.

Background: Transplantation of allogeneic tissues is becoming a wider practice for the replacement of organ function lost to congenital or acquired pathologies. Chronic immunosuppression remains a necessity to prevent organ rejection, despite increased risks of infection, organ toxicity, and malignancies. Abnormalities of female gonadal function in patients of reproductive age are recognized, however, pathological alterations of the reproductive system in patients treated with new generation immunosuppressive drugs are still poorly documented., Methods: We report herein our observations of abnormalities of the reproductive system in 13 female recipients of allogeneic islets for type 1 diabetes, under immunosuppression therapy based on daclizumab induction and tacrolimus/sirolimus maintenance., Results: Menstrual cycle alterations and clinically significant ovarian cysts were frequently observed in our patients, some requiring medical or surgical intervention. All ovarian cysts appeared of benign nature., Conclusions: Our findings suggest that pre- and posttransplant evaluation of female patients should include menstrual history, baseline pelvic ultrasound, and hormonal levels to assess the presence and monitor the progression of such alterations.

Many cell types regulate their volume in response to extracellular tonicity changes through a complex series of adaptive mechanisms. Several methods that are presently used to measure cell volume changes include Coulter counters, fluorescent techniques, electronic impedance, and video microscopy. Although these methods are widely used and accepted, there are limitations associated with each technique. This paper describes a new method to measure changes in cell volume based on the principle that fluid flow within a rigid system is well determined. For this study, cos-7 cells were plated to line the inner lumen of a glass capillary and stimulated to swell or shrink by altering the osmolarity of the perfusing solution. The cell capillary was connected in series with a blank reference capillary, and differential pressure changes across each tube were monitored. The advantages of this method include 1) ability to continuously monitor changes in volume during rapid solution changes, 2) independence from cell morphology, 3) presence of physiological conditions with cell surface contacts and cell-cell interactions, 4) no phototoxic effects such as those associated with fluorescent methods, and 5) ability to report from large populations of cells. With this method, we could detect the previously demonstrated enhanced volume regulation of cells overexpressing the membrane phosphoprotein phospholemman, which has been implicated in osmolyte transport.

A microchip solid-phase extraction method for purification of DNA from biological samples, such as blood, is demonstrated. Silica beads were packed into glass microchips and the beads immobilized with sol-gel to provide a stable and reproducible solid phase onto which DNA could be adsorbed. Optimization of the DNA loading conditions established a higher DNA recovery at pH 6.1 than 7.6. This lower pH also allowed for the flow rate to be increased, resulting in a decrease in extraction time from 25 min to less than 15 min. Using this procedure, template genomic DNA from human whole blood was purified on the microchip platform with the only sample preparation being mixing of the blood with load buffer prior to loading on the microchip device. Comparison between the microchip SPE (microchipSPE) procedure and a commercial microcentrifuge method showed comparable amounts of PCR-amplifiable DNA could be isolated from cultures of Salmonella typhimurium. The greatest potential of the microchipSPE device was illustrated by purifying DNA from spores from the vaccine strain of Bacillus anthracis, where eventual integration of SPE, PCR, and separation on a single microdevice could potentially enable complete detection of the infectious agent in less than 30 min.

The potential for using polyelectrolyte multilayers (PEMs) to provide chromatographic functionality on continuous silica networks created from sol-gel chemistry has been evaluated by capillary electrochromatography (CEC). Construction of the PEM was achieved by flushing the column with polyelectrolytes of alternative charge, with variation of the properties of the exposed polyelectrolyte providing a unique means to vary the chromatographic surface. Variation of the exposed polyelectrolyte from poly(diallyldimethylammonium chloride) (PDDAC) to dextran sulfate (DS) allowed the direction of the electroosmotic flow (EOF) to be changed and also provided a means to vary the chromatographic capacity. Variation of negative polymer from DS to poly(styrene sulfonate) (PSS) significantly altered the EOF and the migration of peptides, with both the reversed-phase and ion-exchange capacities increasing. An alternative method for changing the column capacity was to change the thickness of the PEM, which was evaluated by anion-exchange CEC. A 70-80% increase in retention was observed for all anions without any increase in EOF suggesting significant penetration of the analytes through the PEM and interaction with buried charges within the PEM.

Silica monolithic columns suitable for implementation on microchips have been evaluated by ion-exchange capillary electrochromatography. Two different silica monoliths were created from the alkyl silane, tetramethyl orthosilicate (TMOS), by introducing a water-soluble organic polymer, poly(ethylene oxide) (PEO), with varying molecular weights into the prehydrolyzed sol. Silica monoliths created using 10 kDa PEO were found to have a much more closed gel structure with a smaller percentage of pores in the microm size range than gels created using 100 kDa PEO. Additionally, the size of the mesopores in the 100 kDa PEO monolith was 5 nm, while those in the 10 kDa PEO gel were only 3 nm. This resulted in a strong dependence of the electroosmotic flow (EOF) on the ionic strength of the background electrolyte, with substantial pore flow through the nm size pores observed in the 10 kDa PEO gel. The chromatographic performance of the monolithic columns was evaluated by ion-exchange electrochromatography, with ion-exchange sites introduced via dynamic coating with the cationic polymer, poly(diallyldimethylammonium chloride) (PDDAC). Separating a mixture of inorganic anions, the 10 kDa PEO monolithic columns showed a higher effective capacity than the 100 kDa PEO column.

A silica-based solid-phase extraction system suitable for incorporation into a microchip platform (nu-total analytical system; nu-TAS) would find utility in a variety of genetic analysis protocols, including DNA sequencing. The extraction procedure utilized is based on adsorption of the DNA onto bare silica. The procedure involves three steps: (i) DNA adsorption in the presence of a chaotropic salt, (ii) removal of contaminants with an alcohol/water solution, and (iii) elution of the adsorbed DNA in a small volume of buffer suitable for polymerase chain reaction (PCR) amplification. Multiple approaches for incorporation of this protocol into a microchip were examined with regard to extraction efficiency, reproducibility, stability, and the potential to provide PCR-amplifiable DNA. These included packing microchannels with silica beads only, generating a continuous silica network via sol-gel chemistry, and combinations of these. The optimal approach was found to involve immobilizing silica beads packed into the channel using a sol-gel network. This method allowed for successful extraction and elution of nanogram quantities of DNA in less than 25 min, with the DNA obtained in the elution buffer fraction. Evaluation of the eluted DNA indicated that it was of suitable quality for subsequent amplification by PCR.

Femtosecond thermoreflectance data for thin films and bulk quantities of Au, Cr, and Al are compared with the parabolic two-step thermal diffusion model for the purpose of determining the electron-phonon coupling factor. The thin films were evaporated and sputtered onto different substrates to produce films that vary structurally. The measurement of the electron-phonon coupling factor is shown to be sensitive to grain size and film thickness. The thin-film thermoreflectance data are compared with that of the corresponding bulk material and to a theoretical model relating the coupling rate to the grain-boundary scattering and size effects on the mean free path of the relevant energy carrier.

Background: Mutations in the oncogene ras occur in 20-50% of colorectal cancers. The presence of these mutations allows screening tests to be developed based on the identification of mutant DNA in cells derived from cancers. A study of the prevalence and clinicopathological associations of ras mutations was undertaken., Methods: The frequency of mutations in codons 12 and 13 of the K-ras gene was investigated in 103 colorectal carcinomas using restriction fragment length polymorphism., Results: Mutations were detected in 32% (33/103) of the tumours, predominantly in codon 12 (25/33). No mutations were detected in normal-appearing mucosa from the same patients., Conclusions: Analysis of the frequency of ras mutations compared with various independent clinical variables revealed a sex-linked relationship between the presence of a ras mutation and nodal status but no correlation with any other clinical parameter was found. The findings suggest that screening tests based on ras mutation detection may lack sensitivity because of the presence of mutations in only 32% of tumours.

Snow feedback is expected to amplify global warming caused by increasing concentrations of atmospheric greenhouse gases. The conventional explanation is that a warmer Earth will have less snow cover, resulting in a darker planet that absorbs more solar radiation. An intercomparison of 17 general circulation models, for which perturbations of sea surface temperature were used as a surrogate climate change, suggests that this explanation is overly simplistic. The results instead indicate that additional amplification or moderation may be caused both by cloud interactions and longwave radiation. One measure of this net effect of snow feedback was found to differ markedly among the 17 climate models, ranging from weak negative feedback in some models to strong positive feedback in others.